Spectroscopy illuminator with improved delivery efficiency for high optical density and reduced thermal load

ABSTRACT

An improved illuminator for generating broadband light, and for delivering the light to a sample with an improved delivery efficiency, for higher optical density and/or reduced thermal transfer, than achieved with conventional halogen bulb sources. The illuminator enables spectroscopic analysis in thermally-sensitive or spatially-constrained environments. A phosphor-coated broadband white LED and integrated collimating optics produces a continuous, collimated broadband light beam from 400 nm to 700 nm, which is then transmitted through space to a sample region, such as a living tissue in vivo. A method and system for measuring oxigeneration of mucosal or subsurface tissue is also described.

FIELD OF THE INVENTION

[0001] The present invention relates to illumination devices and systemsfor providing a high efficiency of broadband light delivery tothermally-sensitive or spatially-constrained environments, and moreparticularly relates to the embedding of a light source comprised of awhite, conversion-efficient, narrow-angle, light emitting diode withintegrated collimating and light collection optics into a medicalcatheter for indwelling gastrointestinal placement for the purpose ofperforming real-time in vivo tissue oxygenation measurements of mucosalsurfaces via visible wavelength optical spectroscopy, thus avoiding someof the cost, risk, light level limitations inherent in conventionalilluminator systems.

BACKGROUND OF THE INVENTION

[0002] The traditional broadband light sources for optical spectroscopyin the near UV, visible, and/or near-infrared wavelengths are thefluorescent, incandescent, and arc-lamp bulbs. Typically, spectroscopybulb is optically coupled to the test sample via gratings, lenses,fibers, and/or free-space transfer. However, such traditional lightsources have significant native disadvantages, including that: (a) theyproduce their light rather inefficiently, wasting a large proportion ofthe power supplied to them as heat and unusable wavelengths of light.This is a drawback in devices where significant local heating (such asmedical devices in contact with tissue) or high power consumption (suchas battery operated devices for field use) are undesirable orunacceptable, and (b) they emit light over a wide spherical angle fromnon-point sources, rendering inefficient any attempts to direct theirlight either onto spectroscopy samples (such as living tissue) or intooptical delivery systems (such as fibers coupled to test samples), whichin turn further raises heat production and power consumption for anydesired level of sample illumination.

[0003] These limitations are best appreciated by example. First, withspecific regard to the production of large amounts of heat, conventionalbulbs are inefficient at best. The visible light output from aconventional incandescent light bulb represents only 4% of the totalpower consumed by the bulb. This conversion efficiency rises to only 14%for so-called high-output halogen lamps (though the improved efficiencyresults in accelerated drift and bulb aging). These efficiencies caneasily drop farther, by a factor of 5 or more, if one considers onlyin-band light used in spectroscopic analysis (e.g., a 500-600 nm lightband for hemoglobin analysis) in determination of the conversionefficiency.

[0004] The physical reason for this meager rate of energy conversion isthat tungsten filaments, as well as heated arc lamp electrodes, operateas blackbody thermal radiators, and thus radiate mostly infraredradiation, plus a small component of UV radiation, at any temperaturethey can withstand. While in theory an ideal blackbody radiator producesvisible light most efficiently at 6,600K (11,500° F.), nothing known inthe art remains solid for use as a filament at this temperature, whichexceeds the temperature at the sun's surface. Even so-called“high-efficiency” projection-type halogen lamps must therefore operatefar below this ideal temperature, often operating instead from 2,700K to3,500K (just below Tungsten's melting point of 3,683K). As a result,such bulbs typically require 6.9 W of power to produce 5.9 W of heat, inaddition to 1.0 W of light.

[0005] Such poor conversion efficiencies result in a high degree ofunwanted thermal output, making conventional bulbs run hot, and in turnpreventing close illumination of the sample and often relegatingbulb-based light sources into fiber-coupled hot, external, fan-cooledboxes.

[0006] Second, with regard to the broad spatial emission, conventionalbulbs typically produce light in all directions in the absence ofmirrors or lenses—that is, relatively uniformly over a full 4π sphericalangle. Further, because a filament has a length and width, the light canno longer be focused to a point. This broad spatial emission typicallymakes a direct coupling of light from a conventional bulb onto a sample,or into an optical guide, inefficient. For illustration, consider a 1 cmdiameter spherical bulb in which light from the bulb's filament radiatesevenly in all directions. The glass surface resides approximately 5 mmfrom the filament in all directions, for a surface area of the glasssphere of 4/3*π*r², or 105 mm². The portion of this uniform field ofradiated light reaching a 1 mm diameter sample, placed up against thebulb glass, measures only 0.79 mm². Thus, this tiny sample intercepts(and is thus illuminated by) only 0.2% of the total light output fromthe bulb, as given by the ratio (0.79 mm²/105 mm²), with 99.8% of thebulbs output wasted. The less compact a lamp's source, the moredifficult it becomes to focus and guide its light. This is especiallytrue for UV fluorescent lamps, where focusing losses are far higher thanfor a halogen bulb.

[0007] Further, the surface temperature of a halogen bulb often exceeds120° C., making a close approximation of a hot bulb and sample not wiseor practical in many cases, especially if the sample is living orfragile. Moving the sample away from the bulb, in order to spare thesample from heating, only worsens the inefficiencies described above.Nor is the situation improved by separating the bulb and sample usingoptical fiber. Directly attaching an optical fiber to the glass orquartz surface of 1 cm diameter bulb discussed above (such as by usingoptical glue) allows the fiber to intercept and capture only thosephotons striking the face of the fiber. A fiber measuring only 100microns in diameter has a tiny face area measuring just 0.0079 mm².Thus, a 100 micron fiber, glued to the bulb 5 mm from the filament,collects only 0.002% of the bulb's emitted light, as given by the ratio(0.0079 mm²/105 mm²). Even if the diameter of the fiber in this examplewere to be enlarged 10 fold, this transfer ratio would rise to only 0.2%of the bulb's visible light output that is intercepted and transmittedto the sample, again with 99.8% of the bulbs output lost and wasted.

[0008] All told, when taking into consideration both of the abovelimitations, the poor conversion efficiency of energy to light and thepoor transfer efficiency of light to the sample, only 0.0003% of theenergy flowing into the 1 cm bulb discussed above ends up converted tovisible light, captured, and successfully transmitted by a fiber to atissue sample, for more than 99.9997% of the total light wasted. Here,we term the 0.0003% figure of merit the delivered efficiency. Anotherway of expressing how poor this net delivered efficiency is, in fact, isthat for the preceding bare-fiber-to-bare-bulb example, 369,524 watts ofenergy would have been required by the bulb for each watt of lightdelivered to sample or tissue, with the remainder released and lost asheat. These limitations of conventional sources are apparent in the art.

[0009] Broadband lamp sources or lamp designs are known, and are usedfor spectroscopy. Most art regarding illumination sources forspectroscopy suggest devices or methods that describe conventional lightsources, although some describe more exotic lamp sources (e.g., U.S.Pat. No. RE29,304). White LEDs are known (e.g., U.S. Pat. No. 6,252,254,WO 01/01070), however none are suggested as spectroscopic light sources,and their high conversion efficiency, narrow angle of emission, andoptical stability have not been cited nor exploited for spectroscopypurposes, especially in medicine for in vivo uses, save merely that theyhave been mentioned in passing for the purpose of generalnon-spectroscopic endoscopic illumination (U.S. Pat. No. 6,251,068).Several schemes for reducing heat production or for transmitting lightto a sample are known (e.g., such as light conducting rods in U.S. Pat.No. 5,974,210), but none with the purpose of improving the efficiency ofdelivery, nor are these sources specifically designed to operate as coolspectroscopic illuminators with high delivery efficiency.

[0010] With specific regard to medical probes coupled to or embeddedwith light sources, a number of systems are known. Examples includeinvasive or tissue surface monitoring devices equipped with fiberoptics, such as catheters, needles, and trocars (e.g., U.S. Pat. No.5,280,788, U.S. Pat. No. 5,931,779), as well devices containing thelight source itself (e.g., U.S. Pat. No. 5,645,059, U.S. Pat. No.5,941,822, WO 00/01295). These systems typically completely ignore thecomplex issues of broadband illumination source design, suggesting onlythat known or existing light sources can be used rather than proposingimproved illumination sources, and none of these systems considerspecifically design issues regarding design and deployment of broadbandoptical light sources, especially with regard to conversion efficiency,source efficiency, and heat transfer to the sample, nor do they proposeany specific or novel high delivery efficient optical sources.

[0011] Therefore, all of the above illumination systems and methodssuffer from one or more limitations noted above, in that they are eithernarrow band emitters (such as lasers or filtered spectra), they are notconfigured to deliver light with a high efficiency, they have obligatoryhigh local heating of the sample, they couple relatively poorly betweenthe bulb and tissue or sample, they are not appropriate to be placed inclose proximity to samples, and/or they ignore or omit designconsiderations regarding illumination efficiency and density, and thusfail to reliably provide an improved illumination source for theperformance of spectroscopy in thermally sensitive samples, such asliving tissues, or in spatially constrained geometries, such as throughfibers and needles.

[0012] None of the above systems suggest or teach a method and system tomore efficiently deliver light to tissue or spectroscopy samples withoutdamaging delicate samples, in order to produce a more efficient and/orhigh density illumination for the performance of spectroscopy inthermally sensitive samples, such as living tissues, or in spatiallyconstrained geometries, such as through fibers and needles, such as foridentifying tissue by type or state or for monitoring the oxygenation ofliving tissues, in vivo and in real time. A delivery-optimized, reducedheat, high-density illuminator for real-time in vivo spectroscopicapplications has not been taught, nor has such a tool been successfullycommercialized.

SUMMARY AND OBJECTS OF THE INVENTION

[0013] The present invention relies upon the knowledge of the designconsiderations needed to achieve a high efficiency delivery, highillumination-density broadband illuminator, allowing for reduced powerconsumption and/or heat production (these in turn facilitatingdeployment on or within a spectroscopic lab-on-a-chip, microdevice, ormedical probe) so as to provide improved illumination for spectroscopy,with such benefits as more efficient light delivery, higher deliveredintensities, reduced thermal transfer to the sample, more stable lightlevels, and/or allowing implementation of a light source more simply andinexpensively than has been achieved in a similar device and/orconfiguration using a conventional incandescent light bulb.

[0014] A salient feature of the present invention is that, while theproduction of broadband light is often currently associated with poordelivery efficiency of that light to a target sample, the deliveredoptical power can be beneficially increased through more efficientilluminator design, rather than by merely increasing the power of thelight source (which also can increase heating, reduce stability, andshorten bulb life), and that those design choices include use of bulbswith integrated lenses, high conversion efficiency solid-state white orbroadband LED light sources, and/or lensed optical fiber couplers insuch cases where light must be transmitted by optical fiber.

[0015] Another salient feature is that, while light from a bare orreflectorized conventional bulb couples inefficiently into optical lightguides or onto tissue, the effective light delivery can be improved bythe use of specialized optics deployed within the light bulb or lightsource itself, thus allowing for a high density light delivery usingoptical guides such as fibers, by use of a source with a non-sphericaloutput, or by deploying a low-heat source directly within the medicalprobe or device itself.

[0016] Another salient feature is that, while the production ofbroadband illumination is often accompanied by the production ofsignificant unwanted heat (and that this heat frequently limits how andwhere a light source can be deployed), the waste heat produced for agiven level of desired light incident upon the sample can bebeneficially reduced by light source design choices that reduce theinput power required to deliver a set amount of light power to thesample, such as more efficient coupling of a bulb to a fiber, or fromthe use of lower-heat light sources such as LEDs.

[0017] A final salient feature is recognition that low-heat sourcesfrequently exhibit greater inherent optical stability than theirconventional lamp counterparts, even without stabilizing feedback opticsand electronics.

[0018] Accordingly, an object of the present invention is to provide anoptical illuminator with an improved delivery efficiency over aconventional high-efficiency halogen projection-type bulb—that is, withan overall delivery efficiency at least twice as good, and ideally 25times or more better, than a typically achieved by a comparablefree-space coupled or fiber-coupled halogen bulb.

[0019] Another object of the invention is to provide an improvedillumination density as compared to a conventional high-efficiencyhalogen projection-type bulb—that is, with an illumination density atleast twice that, and ideally 5 times or more better, than typicallyachieved by a conventional bare free-space coupled or fiber-coupledhalogen bulb, most preferably exceeding a continuous visible broadbandpower density of 10 mW/mm² for needle-based illumination for directillumination.

[0020] Another object is to provide a white or broadband LED withsufficiently reduced local heating as to allow integration directly intosmall probes, devices, and even onto spectroscopy lab-on-a-chipmicrochips—that is, with a reduction in heat produced per mW of lightdelivered to the sample by at least 5-fold, and by as much as 200-foldor more, than typically achieved by a conventional bare halogen bulbeither free-space coupled or fiber-coupled to a sample region.

[0021] Another object is to provide for probes and systems withintegrated illuminators, delivery optics, as well as including lightcollection optics to collect and/or transmit light returning afterinteraction with the sample, while still meeting or exceeding theimprovement criteria for improved illuminators as described herein.

[0022] The improved illuminator as described has multiple advantages.

[0023] One advantage is that an illuminator with sufficiently reducedheat production for a given level of target sample illumination may nowbe safely deployed within an instrument in proximity or in contact withsensitive samples, such as for use inside, or in contact with, livingtissue, wherein use of conventional light sources would have otherwiseresulted in thermal tissue injury from the light source, or required thesource intensity to be reduced to such low levels that spectroscopywould have required unacceptably long integration times. In some cases,the improved illuminator may incorporate white LEDs as a light source,with as low as 20 mW of heat produced per mW of usable light deliveredto the sample.

[0024] Another advantage is that bulb light sources can still beemployed, but lens coupled to optical fibers rather than bare-bulbcoupled to fibers, and then the bulb source can be deployed at adistance, to provide high-density light that is delivered relativelyefficiently, as compared to coupling of the same bulb in the absence oftransfer optics, thus requiring substantially less power to achieve agiven power density at the sample. This high-density light can then bedelivered to the sample using an insulating optical fiber, without theneed for cooling of a high-thermal output source near the sample. Thehigh-thermal output light source also can produce less heat due to themore efficient coupling of optical power into the fiber.

[0025] A final advantage is that high-efficiency illuminators, by virtueof their lower power consumption, can in some cases use integrated powersources, such as alkaline batteries, to allow for complete electricalseparation of a probe tip from a medical system connected to the probe,despite the presence of an electrically-powered illuminator on or in thepatient.

[0026] There is provided an illuminator for generating broadband light,and for delivering this light to a sample, with higher efficiency thanconventional bare or fiber coupled light sources, for the purpose ofenabling spectroscopic analysis. In one example, the system uses aphosphor-coated white LED and integrated collimating optics to producecontinuous, broadband light from 400 nm to 700 nm in a collimated beam,which can then be transmitted through free space to a sample, such as atarget tissue, resulting in a high efficiency delivery of light to thetarget tissue. The efficient conversion of power to light, and the highdelivery efficiency, combine to allow this illuminator to remain coolduring operation, further allowing it to be integrated into the tip of amedical instrument, where then broadband illuminator can illuminateliving tissue. Scattered light, returning from the sample, can becollected by an optional optical output fiber, deployed within thesource optics, for transfer and analysis via an optional analysissystem. Medical probes and systems incorporating the improvedilluminator and medical methods of use are also described.

[0027] The breadth of uses and advantages of the present invention arebest understood by example, and by a detailed explanation of theworkings of a constructed apparatus, now in operation and tested inmodel systems, animals, and humans. These and other advantages of theinvention will become apparent when viewed in light of the accompanyingdrawings, examples, and detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

[0028] The following drawings are provided:

[0029]FIG. 1 is a schematic diagram of an illuminator incorporating awhite LED and constructed in accordance with the invention;

[0030]FIG. 2 shows the improved illuminator of FIG. 1 as incorporatedinto a medical catheter;

[0031]FIG. 3 is a drawing of a medical monitor to which the probe ofFIG. 2 is attached to form a complete medical system;

[0032] FIGS. 4A-4D show additional medical probes incorporating theimproved illuminator;

[0033]FIG. 5 is a schematic diagram of an illuminator incorporating aninternally-lensed halogen bulb and constructed in accordance with theinvention;

[0034]FIG. 6 shows the improved illuminator of FIG. 5 as incorporatedinto a medical catheter; and

[0035]FIG. 7 shows data from the colon of a live human subject duringperiods of low arterial oxygen in vivo, as collected and analyzed inreal time by a medical monitor to which the catheter of FIG. 6 isattached.

DEFINITIONS

[0036] For the purposes of this invention, the following definitions areprovided:

[0037] Real Time: A measurement performed in a few minutes or less, andpreferably in under 10 seconds. In medical or surgical use, suchreal-time measurements allow a procedure or a treatment plan to bemodified based upon the results of the measurement.

[0038] In Vivo: A measurement performed on tissues on or within a livinganimal, plant, viral, or bacterial subject.

[0039] Sample: Material illuminated by a light source for spectroscopicanalysis. A sample may be living tissue.

[0040] Tissue: Sample material from a living animal, plant, viral, orbacterial subject, with an emphasis on mammals, especially humans.

[0041] Target Tissue: A tissue or cell type to be detected, imaged, orstudied. In the accompanying examples, one target tissue is humancolonic mucosal capillary hemoglobin, while another is an ablated tumorgrowth.

[0042] Sample or Target Region: A physical region at which a sample ortissue to be analyzed is to be placed. The target region is the areailluminated for spectroscopic analysis.

[0043] Target Tissue Signal: An optical signal specific to the targettissue. This signal may be enhanced through use of a contrast agent.This signal may be produced by scattering, absorbance, phosphorescence,fluorescence, Raman effects, or other known spectroscopy techniques.

[0044] Scattering Sample: Material that scatters light as a significantfeature of the transport of photons through the sample. Most tissues invivo are scattering samples.

[0045] Light: Electromagnetic radiation from ultraviolet to infrared,namely with wavelengths between 10 nm and 100 microns, but especiallythose wavelengths between 200 nm and 2 microns, and more particularlythose wavelengths between 450 and 650 nm.

[0046] Broadband or Broad Spectrum Light: Light produced over a widerange of wavelengths sufficient to perform solution of multiplesimultaneous spectroscopic equations. For tissue, a width of at least 40nm is likely to be needed, while in the preferred embodiment a broadbandwhite LED produces light from 400 nm to beyond 700 nm.

[0047] LED: A light emitting diode.

[0048] White LED: A broadband, visible wavelength LED, often comprisedof a blue LED and a broad-emitting blue-absorbing phosphor that emitsover a wide range of visible wavelengths. Other phosphors can besubstituted, including Lumigen™, as discussed herein. As used in theexamples herein, any broadband LED could be used, even if not emittingover a full (white) spectrum. For example, an LED emitting over a rangeof 100 nm would be considered to be broadband.

[0049] In-Band or Usable Light: Light produced by a light source thatfalls into a specific range of wavelengths used in the spectroscopicanalysis. This band will change, depending upon the analysis desired.For example, a bulb may have reasonable output from 380 nm to 800microns, but only light in the 500-600 nm band may be used for one typeof hemoglobin analysis, while light from 700-800 nm may be used in ananalysis of tissue desaturation during thermal ablation.

[0050] Light Source: A source of illuminating photons. It may becomposed of a simple light bulb, a laser, a flash lamp, an LED, a whiteLED, or another light source or combination of sources, or it may be acomplex form including, a light emitter such as a bulb or light emittingdiode, one or more filter elements, a transmission element such as anintegrated optical fiber, a guidance element such as a reflective prismor internal lens, and other elements intended to enhance the opticalcoupling of the light from the source to the tissue or sample understudy. The light may be generated using electrical input (such as withan LED), optical input (such as a fluorescent dye in a fiber respondingto light), or any other source of energy, internal or external to thesource. The light source may be continuously on, pulsed, or evenanalyzed as time-, frequency-, or spatially-resolved. The light emittermay consist of a single or multiple light emitting elements, such as acombination of different light emitting diodes to produce a spectrum oflight.

[0051] Conventional Light Source: The typical broadband illuminatorlight source cited in the art and/or used in commercial systems is abulb lamp, such as high-efficiency halogen lamp or arc lamp.

[0052] Luminous Flux: The total optical power output of a light sourceover a given spherical angle, usually expressed in Lumens (lm), butintraconvertible with watts or photons per second.

[0053] Luminous Efficiency: The power output of a light source in thedesired wavelength range for a given amount of supplied input power, inLumens of output per Watt of supplied power (Lm/W).

[0054] Conversion Efficiency: As used herein, similar to LuminousEfficiency but expressed as the fraction of input power effectivelyconverted to illumination of the desired waveband. For visible light, aluminous efficiency of 242.5 lumens per watt would represent aconversion efficiency of 100%. Typical conversion efficiencies forincandescent bulbs to visible light are 4-14%, while LEDs can havein-band efficiencies from 10% to well over 40% (about 100 Lm/W) fornewer white LEDs.

[0055] Transfer or Coupling Efficiency: As used herein, the percentageof the total usable light output of a light source that is effectivelydelivered to a finite sample or into a transmission fiber for deliveryto a sample.

[0056] Delivery Efficiency: The fraction or percent of input power to alight source that eventually reaches a target tissue as illumination inthe desired wavelength band. This is a function of both source andcoupling optics, as well as reflects the size of the measured targetarea itself. Also equal to the conversion efficiency multiplied by thetransfer efficiency.

[0057] Optical Density: As used herein, the optical power of usablewavelengths incident upon a target region per unit area, in mW/mm².

[0058] Thermal Load: As used herein, the amount of heat produced for agiven amount of usable delivered optical power, in mW heat per mWdelivered light. This factor indicates how hot a given illuminator willrun during operation in order to deliver a set amount of illuminationrequired. The lower this value, the cooler the illuminator will run toachieve a set amount of delivered illumination of the target sample.

[0059] Transferable Thermal Load: As used herein, similar to thermalload above, but restricted to the heat at risk for transfer to thesample, in mW heat transferable to the target region per mW deliveredlight to the target region. The lower this value, the cooler the samplewill be when achieving a set amount of delivered illumination. Thus, ifa given illuminator is fiber coupled and is physically separated fromthe spectroscopy sample, the transferable thermal load is zero, even ifthe source runs hot, as the heat does not reach nor affect thespectroscopy sample; however, if the illuminator is near the sample,such as in the tip or handle of a medical probe, then part or all ofthis heat is at risk for transfer to the sample, and the transferablethermal load is equal to part or all of the thermal load.

[0060] Negligible Transferable Thermal Load: As used herein, atransferable thermal load of less than 1 mW per mW of delivered light isconsidered negligible.

[0061] Light Detector: A detector that generates a measurable signal inresponse to the light incident on the detector.

[0062] Optical Coupling: The arrangement of two optical elements suchthat light exiting the first element interacts, at least in part, withthe second optical element. This may be free-space (unaided)transmission through air or space, or may require use of interveningoptical elements such as lenses, filters, fused fiber expanders,collimators, concentrators, collectors, optical fibers, prisms, mirrors,or mirrored surfaces. For most optical elements, there is an entry end,where light enters, and an exit end, where light exits. This can also bedefined as a proximal end nearest the light source, and a distal endnearest the sample. These two descriptions are not equivalent, forexample the proximal end of an optical fiber may be the entry or theexit end, depending on whether light in the fiber is traveling toward oraway from a sample region.

DESCRIPTION OF A PREFERRED EMBODIMENT

[0063] One embodiment of the illumination device will now be described.With reference to FIG. 1, the illuminating device or illuminator 103 isillustrated with its component parts. Broad spectrum white light isemitted by a high conversion-efficiency white LED source 105 (in thiscase, The LED Light, model T1-3/4-20 W-a, Fallon, Nev.). Diode source105 is embedded into plastic beam-shaping mount 106 having shaped lensend 107. The plastic is an optically clear epoxy 111 to allow lightgenerated in well 117, emitted over a 20 degree half angle by the diodesource 105, to be collimated, thus remaining at a near-constant diameterafter passing through lens 107. Light then is able to pass forward, in acollimated beam as shown by light path vectors 114, with some to reachand be optically coupled to target region 125 (not a part of illuminator103).

[0064] A portion of the light reaching target 125 is scattered andreflected, and returns as returning scattered and reflected light 128 tocollection fiber 141. Collection fiber 141 is a black-coated opticalfiber and is shielded from stray light from source 105 within the bodyof illuminator 103 by this black coating (not shown). Fiber 141 is inturn secured by optical clear epoxy 157 within channel 159. Fiber 141 isadditionally shielded from stray light at the surface of lens 107 byshallow well 163, which is filled with light-absorbing black epoxy 167.

[0065] Illuminator 103 has two electrical connections 175 and 176, andone optical connection, namely fiber connection 179, the non-patient, ormonitor end, of collection fiber 141. Electrical connections 175 and 176are used to provide power to diode 105, while connection 179 to opticalfiber 141 is used to collect returning light 128, reflected or scatteredfrom target 125, and returning to fiber 141 at the target or patient endof illuminator 103.

[0066] Optionally, polarizing filters 175 and 177 can be placed inparallel or with crossed-axes, in order to select or exclude specularlyreflected light, respectively, based upon retention or loss ofpolarization.

[0067] Illuminator 103 can optionally be embedded within a medicaldevice, as shown with illuminator 103 embedded in medical catheter probe203 (FIG. 2). Probe 203 has patient-end 206, catheter body 207, andmonitor-end 208. In probe 203, flexible probe body 207 consists of asection of US FDA class VI heat shrinkable tubing 214 surroundingmedical grade Tygon™ tubing 217, both of which are further swaged tolight illuminator 103 at swage points 219 near probe patient end 206.Wires 222 and 223, from electrical connections 175 and 176 of source 105of illuminator 103 (as shown FIG. 1) travel through concentric tubes 214and 217, into extension tubing 225, and terminate in plug 229 atpatient-end 208. Optical connection fiber 224, from optical connection179 of source 105 of illuminator 103 (as shown FIG. 1) travels from thepatient tip of probe 203, running parallel with wires 175 and 176 insideconcentric tubes 214 and 217, to terminate in monitor-end plug 229. Plug229 is a reversible connector plug containing electrical connections,optical connections, or a hybrid mix of both.

[0068] Optionally, it may be beneficial (such as less costly) toseparate the optical and electrical terminations of plug 229 into twoplugs, one plug containing only optical connections and the other plugcontaining only electrical connections.

[0069] Another option is that, in lieu of electrical connections forpowering source 105, which leave probe 203 at plug 229, wires 175 and176 may terminate at an internal power source, in this example buttonbattery 237, which can be fully incorporated into the medical probe,providing power to illuminator 103 upon switching of click-on/click-offswitch 239, also incorporated into the body of the probe. In this case,the source power electrical connections at plug 229 may be able to beeliminated from the plug.

[0070] Probe 203 may be “smart” “with optional, chip 241 integrated intoprobe body 207. This chip may retains information useful in theoperation of the device, such as calibration parameters, a referencedatabase, a library of characteristic discriminant features frompreviously identified tissues, and so on, and this information may beaccessible via plug 229. Additionally, information on chip 241 mayinclude probe identification, probe serial number, use history,calibration details, or other information accessible through plug 229.

[0071] Next, again optionally, if light leaks, or is allowed to leak,from an integrated illumination source, this can create a glow in body207 of probe 203 at catheter location 247. If a logo, or other image, isplaced on probe 203 at point 247, the logo will now glow in a darkenedroom, which is an appealing effect.

[0072] Last, as noted, illuminator 103 may be incorporated into amedical device, such as probe 203 as shown in FIG. 2, or it may beincorporated into a medical system, such as medical system 267 as shownin FIG. 3 with probe 203 attached to system 267 via socket 271. Anexample of such a spectroscopic monitoring system is disclosed in U.S.Pat. No. 5,987,346. An example of illuminator 103 incorporated into abattery-operated system for field use is a portable spectrophotometerfor water analysis. In such a case, illuminator 103 may shine directlyon the sample, making both battery life and thermal transfer significantissues; an example of an invasive medical source would be if illuminator103 were incorporated into a medical probe, needle, or catheter, whichis then used internally within the body, such as in the gastrointestinaltract or in a coronary blood vessel. If illuminator 103 remains too warmfor direct tissue contact, then illuminator 103 may be placed in thebody of the medical probe (such as within the cable) but outside of thepatient, or illuminator 103 may be moved into the case of monitor 267itself. In such instances, it may be essential to have a means tostabilize the fiber with respect to light source 105 of illuminator 103,such as plug 229 and socket 271.

[0073] Operation of the device may now be described.

[0074] In this example, illuminator 103 is incorporated into medicalcatheter probe 203, and connected via plug 229 to spectroscopicmonitoring device 267 via socket 271, as shown in FIG. 3. Power to probe203 is provided by monitor 267, which internally induces source 105 ofilluminator 103 to generate light. Initially, patient end 206 of probe203 is covered with standardization cap 245. When spectroscopic monitor267 is switched on using power switch 273, an internal referencespectrum (not shown, but fully disclosed elsewhere, i.e., in U.S. Pat.No. 5,987,346) is collected with standardization cap 245 in place. Next,cap 245 is removed, the probe is placed in contact with tissue, andlight from illuminator 103, embedded in probe 203, reaches target region125, in this case, living human tissue. Collimated light 114 arriving attarget region 125 is scattered and/or reflected, and some portion ofreturning scattered and reflected light 128 light is collected at thedistal, patient end of collection fiber 141 and returned to monitorsystem 267 via the proximal, monitor end of exit fiber 179 ofilluminator 103.

[0075] Examples of optical probes are shown in FIGS. 2, 4A-4D, and 6.FIGS. 2 and 6 show probes best suited to medical endoscopic use, aspreviously described. FIG. 4A-4D show other types of medical illuminatorprobes, such as a targetable injection needle 278 with illuminationcoupling optical fiber 281, light collection optical fiber 282,injection port 284, and cutting edge 286, as shown in FIG. 4A. FIG. 4Bshows catheter 288 with extendable needle 292 controlled by plunger 293,syringe attachment port 295 for injection through catheter 288 to needleinjection port 295, and with illumination fiber 281 and collection fiber282 embedded internally (not shown) into needle 292 in a manner similarto that shown for needle 278, FIG. 4A, with illumination fiber 281connected to plug 297, and detector fiber 282 connected to plug 298, asshown in FIG. 4B. FIG. 4C shows nibbler 300 with illumination fiber 281and collection fiber 282 embedded into jaws 302 and 303, respectively,for simultaneously monitoring and removing tissue. Lastly, scissors 304,FIG. 4D, with illumination fiber 281 and collection fiber 282 embeddedinto the body of scissors 304. The tools shown in FIGS. 4A-4D areintended to be illustrative of the breadth of potential illuminatorprobes. Incorporation of the illuminator of the present invention intoother medical or surgical instruments, spectroscopic and laboratoryprobes, and the like, can easily be accomplished by one skilled in theart, and no undue limitation is intended or implied by omission of otherexamples.

[0076] Of note, when light from a noninvasive or invasive systempenetrates into tissue, the photons traveling between the light sourceand the light detector take a wide range of paths. The present devicetakes advantage of this effect as the scattering provides an averagingand volume sampling function. When detected illumination is measuredafter it has propagated through the tissue over substantiallynon-parallel multiple courses taken through the tissue between the timethe photons are emitted and then detected, many regions of the tissuecan be sampled, not merely the tissue on a narrow line between emissionand detection. This allows a small but important feature, such as a theability to sample the subsurface capillary layer of gastrointestinalmucosa, even if the probe itself is placed 1 cm from the intestinalwall.

[0077] In this embodiment, light source 105 of illuminator 103 receivesits power from electrical inputs 175 and 176. Here, source 105 is awhite LED, source 105 just as easily be any broadband LED, or be apolymer plastic that emits light under the influence of electricalpower, or be a laser with broadening of the waveband via the input fiberimpregnated with fluorescent dye, and so on, provided that source 105meets the technical requirements of the improved illuminator disclosedherein. As is noted in the latter example, non-electrical types of inputare possible—for example, source 105 may be a mixture of fluorescentpolymers embedded in plastic, and source 105 is activated by supplyingexternal light to the source, rather than by applying power.

[0078] Also, as noted earlier, an integrated battery or set of batteriescan provide power from within the device, reducing cost of theconnection tip. An added advantage of this battery-based approach isthat it removes the need for electrical connection to the illuminator,as an added safety feature.

[0079] Illuminator 103 can still be an incandescent bulb, in certaincases, again provided that source 105 still meets the technicalrequirements of the improved illuminator disclosed herein. Integratedlenses in light bulbs allow for a far greater capture of light,improving the efficiency of the bulb and yielding high photon densitiesat the exit of the fiber. In this manner, a 15W bulb can be used tosupply power equal to, or more than, that of a 125W projector bulb. FIG.5 is an example of this type of bulb-based illuminator. White light bulb305 with filament 307 near integrated lens 309 produces collimated beam313. In this embodiment, bulb 305 receives its power from electricalinputs 316 and 318. Collimated beam 313 is then refocused by reversedbeam expander 324 onto entry 333 of fiber 335, with fiber 335 heldstable and aligned in detachable fiber holder 341, all held together insupporting socket and block 347.

[0080] Since the illuminator of FIG. 5 operates at a high temperature,the illuminator would be deployed in medical monitor 267 away from thepatient. In this case, block 347 is a heat-conductive metal to allow forheat sinking of block 347 to the frame of monitor 267.

[0081] Medical probes that connect to this illuminator would not requireintegrated light sources, rather they would couple light from abulb-based illuminator, such as the illuminator shown in FIG. 5, to thetarget region using optical fibers. In FIG. 6, a medical probe modifiedto removably connect to the optical illuminator of FIG. 5 is shown. Asnoted, medical catheter 403 no longer contains an integratedillumination system. Probe 403 has patient-end 407, catheter body 408,and monitor-and-illumination-end 409. In probe 403, flexible probe body408 consists of a section of US FDA class VI heat shrinkable tubing 414surrounding medical grade Tygon™ tubing 417. Optical illumination fiber424 and optical collection fiber 425, travel from patient tip 407 ofcatheter probe 403, running through catheter body 408 inside concentrictubes 414 and 417, to terminate at plug 429 of monitor end 409. Plug 429is a reversible connector plug containing electrical connections,optical connections, or a hybrid mix of both (in this case, only opticalconnections are present).

[0082] At patient end 407 of catheter 403, optical illumination fiber424 emits light toward a target region. Light reaching sample tissue inthis region, is scattered, absorbed, rotated, re-emitted, and interactedwith in multiple ways. A portion of this light returns to opticalcollection fiber 425, where it is transmitted to medical monitor 267,for processing and analysis, via plug 429 connecting to socket 271 ofmonitor system 267.

[0083] Catheter 403 has several advantages over catheter 203. First,there are no electrical connections to the patient required, reducingthe risk of electrical injury, such as burns or myocardial fibrillation.Another advantage is that the catheter diameter can be much smaller thatcan be achieved with an integrated illuminator, as optical fibers maymeasure only 100 microns in diameter, while light sources measure amillimeter to several centimeters in width.

EXAMPLES

[0084] The breadth of uses of the present invention is best understoodby example, seven of which are provided below. These examples are by nomeans intended to be inclusive of all uses and applications of theapparatus, merely to serve as case studies by which a person, skilled inthe art, can better appreciate the methods of utilizing, and the scopeof, such a device.

Example 1

[0085] Improved Delivery Via Improved Conversion Efficiency

[0086] One method to improve effective delivery efficiency is to improvethe conversion efficiency—that is, to reduce the amount of power neededto produce a given amount of usable light.

[0087] In order to evaluate the impact of design considerations, wemodeled the expected improvement in the efficiency of light deliveryachieved by altering various aspects of an illumination source design,and then verified our model data using experiments. This modelincorporated known features of light generation from tungsten fiberlamps with and without halogen recycle, the transmission characteristicsof certain optical fibers, known general characteristics of broadbandlight emitting diodes (LEDs), and each aspect of the model was tested inthe laboratory to confirm agreement of the predictions to those ofmeasured results.

[0088] First, we considered a high efficiency halogen light bulbfree-space coupled to a tissue sample—that is, illuminated in air andwithout intervening optics. When operating at halogen lamp temperatures(3650K filament, 120-140° C. bulb), a good lamp will configured ideallyproduces 14 Lm/W. For this modeling, we assume that the bulb filament isinfinitesimally small, such that the intensity of the light over anysample is given by the bulb's light output times the fraction of asphere (with a center at the filament and a surface at the sample) thatis intercepted by the sample. The highest theoretical limit for lightdelivery to a sample would be either placing the filament against thesample. Of course, doing so would damage many types of samples, and oneobject of this invention is to increase the delivery efficiency of lightwhile maintaining reduced or safe thermal transfer to the sample.Therefore we have assumed a lamp to tissue distance of 50 mm as aminimum, in order to allow for thermal shielding and heat sinking, withthe lamp illuminating a 10 mm diameter circular target area.

[0089] Using calculations similar to those presented in the backgroundsection, a 15W lamp halogen lamp is now modeled. In practice, increasingthe wattage of the lamp increases the heat output of the bulb, and thusincreases the distance the bulb needs to be from the sample, in order toprotect the sample, and therefore does not result in better illuminationof the sample. At a conversion efficiency of 14% for halogen projectionlamps at 3600K, 12.9W is lost as heat while 2.1W is converted to usablelight. A large circular target, measuring 10 mm in diameter, isconsidered, which intercepts light over an area of 79 mm² (assuming aflat target). This intercept area is taken from a total emission over asphere, with the center at the filament and the surface at the target 50mm from the filament (due to distance kept due to the heat produced),measures 2,618 mm², for a free-space transfer efficiency of 3.0%.Combined with the halogen conversion efficiency, this results in a netdelivery efficiency of 0.4%, with 63 mW delivered to the sample and with205 mW of heat produced for each mW of visible light delivered to thetarget. The intensity of visible light falling on the circular targetsample is 0.80 mW/mm². However, because of the high heat production andsurface temperatures exceeding 120° C., such a bulb is difficult tointegrate directly into an invasive probe or catheter, or deploy on asolid-state device such as in integrated circuit, nor is a 5 cmillumination distance always achievable, such as when a catheter isplaced inside the body or when an illuminator is deployed on anintegrated circuit.

[0090] Next, we considered alternative sources of broadband light withmore efficient conversion of energy to light, for example,phosphor-based broadband LEDs known as a white LEDs. As a device group,LEDs are, in general, more efficient converters for several reasons, asfollows:

[0091] First, LEDs, including white LEDs, produce light more efficientlythan halogen bulbs. The conversion efficiency of an LED can run higherthan 50%, but typically run 25-40%, which is 2 to 3 times the efficiencyof a good halogen bulb.

[0092] Second, LED's, again including white LEDs, tend to emit lightconcentrated into a narrower range of wavelengths than bulbs, and thusthey produce more usable in-band light, with less wastage outside ofthat range, and therefore tend to be more effectively brighter than fora halogen bulb operating with the same total light output.

[0093] Third, an important feature of LEDs in general, including manywhite LEDs and laser LEDs, is that they can emit light over a narrowerrange of spatial angles (e.g., non-uniform non-spherical output). Thus,the light that is produced may be more concentrated in space, andtherefore more usable for spectroscopy, than a conventional bulb.

[0094] Fourth and last, recall that an improvement in efficiency allowsless energy to be used, which results in less heat, allowing the LED tobe moved closer to the sample, and so on, with an exponential reductionin heat and effective illumination produced.

[0095] The net effect of this improvement in conversion efficiency isthat it allows closer placement of the light source to the sample, andthis can be seen by repeating the above calculations for a white LED.

[0096] For comparison to the halogen bulb, consider a white LED with acurrent of 50 mA with a 3 V drop across the diode, for a powerconsumption of 150 mW. As an LED has no requirement for the high bulbtemperatures required by halogen recycle, the surface of the LED packagecan remain cool to warm to the touch. This low temperature allows theLED to be brought nearly in contact with the sample, if needed,delivering even higher light levels and allowing for further powerreductions. For this example, we assume that the LED-based illuminatorat the same 50 mm distance from the sample used for the halogen bulbcalculations earlier in this example.

[0097] The power consumed by the LED in this example, 150 mW, is 100times less power required for the 15W projection bulb discussed above.White LEDs can reach efficiencies of 40% or more, but for this examplewe assume an efficiency of 25%. At this efficiency, the white LED emits63 mW of light while producing 188 mW of heat. Because LEDs emit over anarrow angle, the size of the emitting surface can be small, and LEDsoften have their plastic packaging formed in the shape of a collimatinglens very near the emission source, a large degree of the LEDs light canbe captured and projected into a narrow collimated beam. In theory, themajority or all of the emitted light may be captured and transferredfrom a white LED with a forward-directed reflectorized hemisphericillumination chamber and collimation optics, while in practice thisnumber is likely to be 10-50% or less unless a laser diode is used. Forthis example, we estimate a transfer efficiency of nearly 20%, for a netdelivery efficiency of 4-5%. This net delivery efficiency is over 10times higher than the comparable projection bulb at the same 50 mmdistance.

[0098] As a result, the white LED delivers 7 mW of usable light to thesample area—over 10% of the light level as the 63 mW delivered by a bare15 W projection bulb at 5 cm distance, but with only 16 mW heat producedper mW of light delivered to the tissue, rather than 205 mW heatproduced by the halogen bulb per mW of light delivered. Use of the WhiteLED therefore results in an 11-fold improvement in delivery efficiencyand a 114-fold reduction in heat produced to achieve comparableillumination levels at the tissue target. This allows direct embeddingof a white-LED illumination source into medical catheters and probes,and placement of a white LED directly onto lab-on-a-chip configurations.TABLE 1 Broadband Free-Space Coupling for Halogen Bulb vs. White LED.For free-space illumination, these results are summarized in the tablebelow: Trans- ferable Thermal 1 cm Load Field (mW heat Type ofConversion Coupling Delivery Inten- per mW Illuminator EfficiencyEfficiency Efficiency sity Delivered Source (%) (%) (%) (mW) Light)Conventional  4%  3% 0.12% 18.0 800 mW Bulb Halogen 14%  3% 0.42% 63.0205 mW Bulb White LED 25% 19% 4.69%  7.0  16 mW Improvement 1.8× 6.2×11× 0.11× 12.8× of White LED over Halogen in Probe

[0099] In the example in Table 1, the bulb and LED sources are placed at50 mm distance from the sample due to heat production; though for thelow heat production from the LEDs would allow them to be placed muchcloser, even down to several millimeters from the sample, which wouldresult in reduced transfer losses and lead to further improvement in netdelivery efficiency. In fact, when brought within 1 mm of a sample, thewhite LED has a measured light density over 15 times greater than thatof a halogen bulb at 5 cm, but without the limitations on source andsample separation due to heat produced.

[0100] The performance of a white LED can be even better than the abovediscussion suggests. A white LED is a relatively narrow-spectrumbroadband emitter, unlike a conventional bulb which radiates over a widerange of wavelengths. If only a narrow portion of the spectrum isrequired, the efficiencies of Table 1 above are amplified. For instance,consider a hemoglobin analysis that requires only the wavelengths of500-600 nm. In this case, the usable light from a bulb sources is notthe sum total of the visible light produced with 14% conversionefficiency, but rather only a narrow waveband of this light producedwith only 2.8% efficiency in the halogen lamp. This reduces the netin-band delivery efficiency to 0.08%, making the LED substantiallybetter in light density and heat produced per mW usable light. In thiscase, for a hemoglobin analysis which requires only 500-600 nm light, awhite in-band LED is 56-fold as delivery efficient as a conventionalbulb, with a 64-fold reduction in heat produced at the probe for everymW of in-band light generated, as shown in Table 2, below: TABLE 2In-Band Free-Space Coupling For Halogen Bulb vs. White LED. Type ofConversion Coupling Delivery 1 cm Field Trans. Thermal Load IlluminatorEfficiency Efficiency Efficiency Intensity (Heat Delivered per Source(In-Band %) (%) (%) (mW) mW Light Delivered) Halogen Bulb 2.8%  3% 0.08%12.6 1010 mW White LED  25% 19% 4.69%  7.0  16 mW Improvement 8.9× 6.3×56× 0.56× 64× Using White LED

[0101] Use of a white LED has several specific advantages. A firstadvantage is that cool, high-delivery sources such as diodes and plasticcoupling optics are sufficiently inexpensive so as to make the devicedisposable, resulting in a reduction in risk of infection or driftduring resterilization. Also, the cost of many meters of coated opticalfiber for coupling an illuminator to a medical probe may exceed the costof white LEDs, even without fiber termination and polishing costsconsidered, and thus switching to an embedded white LED can lead to costsavings.

[0102] Another advantage is that the diode illumination source may berapidly switched on and off, providing the ability to obtain real-timeestimates of background illumination.

[0103] Another advantage is diodes tend to be more stable light sourcesthan incandescent lamps, reducing drift in the source intensity, andallowing for calibration at the factory rather than in the field. Thiselimination of calibration and/or stabilization during use can greatlysimply use of a medical probe containing an embedded white LED. Further,an LED may be placed into a disposable or reusable probe with therealistic explanation that bulb failure is highly unlikely.

[0104] Another advantage is the relative coolness of the white LED mayallow improved spectroscopic light sources to be produced withsufficiently low heat production that they can be safely deployed withina probe itself, such as within a spectroscopically-enabled medicalinstrument or upon a self-contained laboratory-on-a-chip.

[0105] Use of a white LED is novel for medical probe or for an on-chipspectroscopy 25 purposes, and has not been previously disclosed, and thedegree of the improvement in transfer efficiency is unexpected fromcasual considerations.

Example 2

[0106] Measurement Using LED and Bulb-Based Probes

[0107] In order to test the validity of the data generated using themodel shown in Example 1, we constructed two working probe types, oneset using a halogen bulb and a second set using a white LED. Lightincident on a tissue phantom was then measured using a silicon-basedphotodiode system (EXFO, model FOT-50, Quebec, Canada).

[0108] In these measurements, the skin was illuminated using the 15Whalogen bulb and the 250 mW white light LED described in the preferredembodiment. Light returning from the skin was collected using a 3.5 mmdiameter circular aperture and measured in overall intensity from 400 nmto 1100 nm.

[0109] Results for in-band free-space illumination are shown in Table 3,below: TABLE 3 Measured Broadband Free-Space Coupling For Bulb vs. WhiteLED. Trans. Max Thermal Type of 1 cm Field Bulb Load (mW IlluminatorCurrent Voltage Power Intensity Temp Heat/ Source (mA) (V) (mW) (mW) (°C.) Light/cm²) Halogen 1120 8.2 9180 1.66 143 4756 Bulb White LED 50 3.4170 0.71 31 180 Improvement 54× 0.42× 26× of White LED over Halogen

[0110] The 26-fold reduction in transferable thermal load is, withinexperimental error, in agreement with the projected improvement of64-fold. The relative low power delivered to the field for both thehalogen and the white LED (10-15% of projected values in Table 2),suggest losses not accounted for (such as surface reflections and otherlosses), or poor coupling of the light into the optical power meter. Thecentral result is not affect, however, as the relative improvements seenremain accurate.

[0111] Importantly, we have achieved a central goal of the improvedillumination source: improved delivery efficiency with sufficientreduction in power required that the device could operate internally inthe body, or in contact with living tissue. In the above study, thedecrease in operating power for the LED was a 54-fold reduction inpower, as compared when using the halogen bulb. This reduction was dueto improved conversion of power to usable light, as well as due to thereduced spatial emissions of the white LED device due to the integratedcup and lens. As a result, the transferable thermal load is also greatlyreduced. In this example, the operating temperature of the LED probe was31° C., in a 21° C. room, which is well below the temperature of thehuman body (37° C.). In contrast, the halogen bulb operated at atemperature sufficiently high to boil water, and were the halogen bulbto operate even 70 degrees cooler, it would still be sufficiently hot tofry an egg. Thus, the LED, though improved conversion of power to usablelight, has allowed construction of a biologically-safe probe, whereasuse of the halogen bulb in tissue could be dangerous.

Example 3

[0112] Improved Delivery Via Improved Transfer Efficiency

[0113] An alternative method for improving the net efficiency of lightdelivery is to improve the coupling of the light source to the sample,measured by transfer efficiency.

[0114] For this example, we considered again a bright halogenprojection-type bulb, too hot to put directly next to a sample such astissue, and in this case even too hot to be safely placed into thehandle or tip of a device such as a medical probe.

[0115] One way to get around the heat issue is to fiber-couple the bulbto the sample, thus removing the inefficient and hot light emitter fromthe vicinity of the sample. As the conversion efficiency of ahigh-efficiency halogen bulb is difficult to modify, improving thedelivery efficiency represents an approachable way for increasing thenet transfer efficiency.

[0116] As noted, the best coupling of light would occur in theory if thefiber could be placed in contact with the filament itself, as this iswhere the sphere of light from the filament is smallest and where thesurface of that sphere has the highest power density. While this cannotbe achieved in practice, as the fiber would melt, the fiber can beoptically coupled to the filament in effectively the same manner, with areduced risk of melting, by using lenses, mirrors, or other opticalfocusing and transmission devices. Certain constraints apply, such aslight cannot be concentrated to a higher density than exists at thefilament using such lenses and mirrors (an exception to this are NIOCs,non-imaging optical collimators, but the wide angles of photons exitingthese NIOC devices can make concentration of photons difficult in somecases), but power densities near the filament power density limit can beapproximated if the majority of the bulb power is redirected using areflector (e.g., posteriorly) and/or lens (e.g., anteriorly).

[0117] In practice, a lens outside the bulb must be large, in order tocapture a significant fraction of the photons leaving the filament. Asan alternative, a lens can easily be integrated into the bulb or bulbglass, capturing a wide angle of forward-directed photons andcollimating or focusing these photons. We model a two-lens system inwhich a lens is integrated into the bulb housing only 2 mm from thefilament, thus collimating and capturing many of the forward-directedphotons, while a second reverse-expander takes this collimated light andcreates a more dense, collimated beam, the size of the optical fiber orsmaller, on the photon entry end of the transmission fiber. Theintegrated lens is part of the bulb's glass, and is designed to operateat a far higher temperature than the layered glass used in a glassoptical fiber.

[0118] Following the form of the calculations presented in thebackground section and Example 1, an optical fiber was initially modeledin the absence of lenses, attached to a 15W lamp halogen lamp. Inpractice, increasing the wattage of the lamp increases the physical sizeof the filament and the distance of the fiber from the bulb, and doesnot result in better illumination of the fiber. At a conversionefficiency of 14% visible light output for halogen projection lampsoperating at 3600K, 12.9 W is lost as heat while 2.1 W is converted tovisible light. For this example, we assume that the fiber is safe fromdamage when placed at a minimum 10 mm from the filament, and we assumeuse of a 100-micron diameter core fiber with a capture half-angle of 20degrees. This fiber, as discussed in the background section, interceptsphotons from the bulb over an area of 0.0079 mm² from a total sphere ofuniform light 10 mm in diameter and with a surface area of 105 mm², fora transfer efficiency of 0.0078% (Table 4). Together with a conversionefficiency of 14%, this yields a net delivery efficiency of 0.0011%,with 0.16 mW delivered to the sample, and 82,000 mW of heat produced foreach mW of light delivered. Despite the high heat production, this lightsource remains cool at the fiber end closest to the sample, and thisfiber end can even be placed against delicate samples, such as if thefiber were to be deployed in a needle configuration. A high powerdensity is achieved at the exit of the illumination fiber of 20.1mW/mm², as shown below in Table 4.

[0119] Now, consider instead a lens-coupled bulb attached to a deliveryfiber. The arrangement is as shown in FIG. 5, with a collimating lensplaced 3 mm from the filament, and reverse expanders for capture of thiscollimated light into optical fibers. Modeling of this arrangement showsa significant improvement in the efficiency of light delivery, as shownin Table 4, below. TABLE 4 Fiber-Based Coupling Without and WithIntegrated Transfer Lenses. Type of Thermal Light Load Source (Heat(fiber- Spot Produced coupled 10 Conversion Coupling Delivery Densityper mW mm from Efficiency Efficiency Efficiency (mW/ Light filament) (%)(%) (%) mm²) Delivered) Halogen 14% 0.0075% 0.0011% 20.1 82,000 Bulb mWw/o Lens Halogen 14% 0.0833% 0.0117% 223  7,400 Bulb mW w/Lens White LED25%    75%    18% 36   675 w/lens mW Improvement 1× 11× 11× 11× 11× forHalogen Using Lens

[0120] In the table above, use of an integrated transfer lens with ahigh-efficiency halogen bulb results in a 11-fold improvement indelivery efficiency, and therefore a 11-fold reduction in the powerrequired, and heat produced, to achieve comparable illumination levelsat the tissue target. In this case, the light source is coupled to thesample via an optical fiber, and therefore none of the heat in eithercase would be transmitted to the sample (though if the bulb is deployedin the handle of a probe, reduced heat remains advantageous). However,from power considerations, reduced power is helpful in situations inwhich power sources are limited, such as in a battery-operated deviceemployed in fieldwork. Here, a reduced power source would offer asignificant extension of battery life, as much as 11-fold longer life inthis case.

[0121] Of practical importance, this model suggests that the lightdensity of the spot exiting the fiber is higher with than without thetransfer lenses. A high density is important when delivering light viafibers, either as illumination to an area via free-space coupling, aswell as when there is an aperture limitation, such as a needle, intowhich as much light as possible is to be transmitted to the tissuesample. In such needles and probes, free space transfer from the bulb tothe sample is not possible, and therefore light input to the sample islimited by the light density within the delivery optics.

[0122] Note that excess heat production impacts and reduces lightproduction, as a hot light source necessitates that the lamp must thenbe moved farther from the sample, which in turn results in additionalcoupling losses which in further necessitate a higher powered bulb, andso on. However, once a decision is made to fiber-couple the source, thelight densities achieved into the fiber via lens coupling will work tominimize the input power required to meet a achieve a given sampleillumination output power at the sample end of the fiber.

[0123] Note also that for some bulb types, such as a halogen lamp, highheat output is an inherent requirement of proper bulb operation, as thebulb's internal glass surface temperature must be at 120-140° C. inorder to allow for halogen recycling to occur, and for the filament totolerate the high operating temperatures. However, again due to the highdensity of broadband light achievable, this may be the preferred optionfor needle-based probes.

[0124] Last, a white LED light source can be similarly connected viafiber, as will be tested in the following example.

Example 4

[0125] Measurement Using Fiber-Coupled Bulb with and without TransferLenses

[0126] In order to test the validity of the data generated using thelens-coupled fiber model shown in Example 3, we constructed fourfiber-based test probes: two using halogen bulbs (with and without lenstransfer optics), and two using a white LED (again, with and withouttransfer optics). We then tested these probes for the light densitypassed into the optical fiber, in order to calculate the true effect ofthe transfer lenses.

[0127] In these measurements, an optical fiber was illuminated using abare 15W halogen bulb run at 5.6W, or with a 150 mW white LED run at 70mW, each tested both with and without an integrated lens and externalcollimating optics. Light collected by the fiber was measured foroverall intensity from 400 nm to 1100 nm using the silicon-basedphotodiode system used in Example 2. Results are shown in Table 5,below: TABLE 5 Measured Improvement in Lens-Coupled Fiber Light Levels.Halogen Lamp White LED (mW/100 μm fiber) (mW/100 μm fiber) No Lens 0.12mW  0.0004 mW With Lens and Collimator 1.20 mW  0.0181 mW Improvement inDelivery 9.8x 45.2x Efficiency

[0128] The above-measured improvements in delivery efficiency are,within experimental error, in agreement with the projected ratio of an11-fold improvement. Of note, the spot density of the light from ahalogen bulb, collected through an optical fiber, was 152 mW/mm², inagreement with Table 1 and up from 15.7 mW/mm² without the transfer lensoptics. This yields an improvement of nearly 10-fold. For the white LED,the transfer optics generates a spot density of 2.3 mW/mm², which shouldrise to over 10 mW/mm² at higher operating currents. In the case of theLED, the improvement using transfer and coupling lenses was over 46fold.

[0129] Importantly, we have again achieved a central goal of theimproved illumination source: the ability to increase the efficiency ofdelivery to produce a higher-density, reduced thermal load source. Inthis case, we used improved coupling so that the density of the opticalspot has been increased 10- to 46-fold (with a resulting spot density ofat least 10 mW/mm², and potentially 100-500 mW/mm² or higher), whiledelivering this illumination through an insulating optical fiber suchthat the net heat delivery to the sample is negligible. Thus, the use ofcoupling lenses, to increased the transfer efficiency, coupled tofibers, to provide thermal insulation, has allowed construction of abiologically-safe illumination source achieving nearly the same densityof light delivery as the deployment of a bulb directly into the probe,but without the danger that may come with such deployment of a hot bulbinto the body or near a delicate sample.

[0130] Last, consider the interest in illuminating a 1 cm diameter areausing light from either a 100 micron optical fiber versus directillumination with a white LED. In such a case, the advantage of thewhite LED is clear, as shown in Table 6: TABLE 6 Comparison of white LEDand fiber illumination of 1 cm tissue region Type of 1 cm Field ThermalLoad Illuminator Intensity Delivery (mW Heat/ Source Power (mW) (mW)Efficiency Light/cm²) Halogen Bulb 9180 1.20 mW 0.01% 7400 w/Fibers andTransfer Lenses White LED  170 3.56 mW 2.09%  35 w/Lens Improvement of 54x 3.0x 160x  211x White LED over Halogen

[0131] In the table above, use of a white LED, rather than a fiber-basedillumination probe, has increased the delivery efficiency 160-fold,reduced power consumption 54-fold, without raising the transferablethermal load above a physiologically tolerable level.

Example 5

[0132] Monitoring Gastric Oxygenation Using a Lensed Fiber-Coupled LightSource.

[0133] Illuminators, constructed in accordance with the presentinvention, were tested in human and animal subjects with institutionalanimal and human review board approval, as appropriate.

[0134] The illuminator of FIG. 5 was incorporated into medical system267. Fiber-optic-based catheter probe 403, designed for endoscopic use,was constructed as shown in FIG. 6. A connector 429 connects thecatheter 403 to illuminator 347 via socket 333, with socket 333 andfiber 424 (335) receiving the illumination as shown in FIG. 5. Oncross-sectional view, catheter 403 has core illumination fiber 424 andlight return fiber 425, all contained within Teflon sheath 414 andtubing 417, 424 and 425 polished and exposed to the patient as fiberends 434 and 437, respectively. Fiber ends 434 and 437 are held at adistance of 1 to 20 mm from the mucosal surface, and estimates ofmucosal oxygenation are made through analysis of the light captured andreturned along fiber 425, for example using the spectroscopic monitoringdevice disclosed in U.S. Pat. No. 6,167,297.

[0135] Catheter 403 was then used, under Human Internal Review Boardapproval, during collection of data from various regions of theesophagus, stomach, intestine, and colon in live human subjects.

[0136] Normal values were collected from multiple subjects. The resultsfrom 29 subjects, with multiple tests taken in most subjects, aresummarized below in Table 7, as follows: TABLE 7 Colon Oxygenation in 29Human Subjects Using a Lens-Coupled Catheter. Number of Total No. ofTests Location Subjects (N) (M) Mean +/− S.D. Esophagus 10 66 61% +/− 4%Stomach 10 121 64% +/− 5% Cecum 4 23 68% +/− 1% Colon (proximal) 10 6765% +/− 4% Colon (transverse) 11 60 65% +/− 4% Colon (distal, sigmoid)15 94 64% +/− 6% Rectum 18 161 66% +/− 3% SUMMARY ALL 29 592 64% +/− 3%REGIONS

[0137] These gastrointestinal data show a high degree of correlation anda tight range of mucosal oxygenation values in the gastrointestinaltract of healthy human subjects. The tight standard deviation for humangastrointestinal mucosal tissue oxygenation suggests that this is arobust value in healthy subjects. For example, values in the colon orrectum below 60% (using this algorithm and analysis) are automaticallymore than 2 s.d. below the mean, should be considered as improbably lowin normal colon tissue.

[0138] We further tested this probe under two conditions that altertissue oxygenation and induce hypoxia: hypoxemia (low arterial bloodsaturation) and ischemia (normal arterial oxygenation with low oxygendelivery due to impaired blood flow or low hematocrit).

[0139] In hypoxemia, colon oxygenation as measured by the catheter waswell correlated with pulse oximetry, as would be expected (r=0.99, datanot shown).

[0140] In ischemia, produced by clamping of major arterial supply to thedistal colon, the catheter was able to detect lowered arterialoxygenation despite an absence of deoxygenation of the arterial blood(not shown). Similar results are seen in the monitoring of small colonprojections, called polyps, as the arterial blood supply wasinterrupted, and ischemia produced, by either injections of epinephrineor vascular tie-off. Ischemia was well detected by the catheter, withoutany effect from saline control injections, as follows: TABLE 8 ColonPolyp Oxygenation During Ischemia Oxygenation Polyp Intervention (Mean+/− SD) No. of Test Normal 63% +/− 6% 26 Vascular Tie-Off  8% +/−3% 8Epinephrine Injection  6% +/− 6% 16 C ntrol (Saline Injecti n) 68% +/−2% 4

[0141] As another example of ischemia, the average mucosal oxygensaturation standard deviation was 3.5%, as shown previously in Table 7.Table 9 (below) shows the measurement results from an asymptomatic61-year-old patient who had undergone a partial colectomy 5 yearspreviously for cancer (an adenocarcinoma). During the operation, 15 cmof sigmoid colon were resected and the inferior mesenteric artery wassacrificed and removed. The surveillance colonoscopy demonstrated anintact anastomosis of the rejoined colon sections, 25 cm from therectum, with approximately 10 cm of normal-appearing sigmoid colondistal to the anastomosis. The measured mucosal saturation in theremaining portion of the sigmoid colon, which had been supplied by theinferior mesenteric artery, now removed, was 47%. This value is 17%below normal (p<0.001). In contrast, measurements in regions of thecolon showed higher oxygenation values the farther from the sacrificedartery one measured. At some distance from the lost artery, where thecolonic circulation had not been disturbed, the measured saturationvalues were normal. This is shown as follows: TABLE 9 Saturation ofcolon in a man with a surgically interrupted inferior mesenteric artery(IMA). Region Saturation Ascending Colon 63% Transverse Colon 65%Anastomosis  57%* Sigmoid Colon  49%* Rectum 61%

[0142] As a final example of ischemia, there is a gradual and developingischemia induced by injection of epinephrine into a polyp. In this case,an intervention (injection) has caused the flow of blood in the tissueto fall, leading to a gradual drop in oxygenation over time. Thus, thesystem can be used to monitor a medical intervention, and detect changesin oxygenation that warn of impending tissue injury. The drop inoxygenation after injection with epinephrine is shown in Table 10, asfollows: TABLE 10 Oxygenation falling in a polyp after an interventionalinjection of epinephrine. The oxygenation values fall after injection,falling to nearly zero after additional time has passed (not shown). Thevalues do not fall completely to zero as a small amount of oxygen isabsorbed from the air. After the tissue dies, the saturation values mayrise, as oxygen is absorbed from the air, but it is no longermetabolized by the tissue. Time After Injection Saturation (sec) (%)Injection 64%  30 sec 54%  60 sec 49%  90 sec 30% 120 sec 25% 180 sec17%

[0143] Thus, we have shown that a colon device could detect bothhypoxemia and ischemia. The gastrointestinal tract is important as it isa central organ, and more closely approximates oxygen delivery to thebody's core organs than does peripheral arterial oxygenation. Also, manyinterventional procedures affect gastrointestinal oxygenation, thus theability to measure this value is likely to have medical value. Last,central organs are more likely to be less sensitive to motion, cold, andother factors that interfere with conventional oximetry. Sites ofmeasurement in the gastrointestinal system could reasonably include theoropharynx, nasopharynx, esophagus, stomach, duodenum, ileum, colon, orother gastrointestinal tissues.

[0144] This system has multiple advantages over conventional pulseoximetry. First, the signal does not require a pulse in order tooperate. Second, as the signal analyzed is not a pulse, but rather thefull returning signal, the signal is inherently less noisy that theAC-extracted-from-total signal of pulse oximetry, in which the ACcomponent tends to represent less than 1% of the total signal. Becauseof this, estimates for met-hemoglobin, carboxy-hemoglobin, and otherblood components may be more easily accomplished.

[0145] In the above examples, the signal detected from the tissue was anabsorbance signal. While absorbance is ideal for hemoglobin analysis, asdescribed in the preferred embodiment, other interactions may bepreferable for other measurements. The interaction with the illuminatinglight that provides the contrast can include absorbance, polarization,optical rotation, scattering, fluorescence, Raman effects,phosphorescence, or fluorescence decay, and measures of a contrasteffect may reasonably include one or more of these effects. For example,a coronary artery catheter could use a dye to report on inflammation orhyperthermia, suggestive of unstable arterial plaque. This could occurby use of native emissions, or the signal could be enhanced, for exampleby detecting the presence of a dye which differentially accumulates inunstable plaque, or which exhibits a dye shift based upon temperature ofthe inflamed tissue.

Example 6

[0146] Measurement of Tissue Oxygenation Using White LED Probe

[0147] In order to further test the validity of the data generated usingthe model shown in Example 1, we constructed additional working probesbased upon an embedded white LED as illustrated in FIG. 2 and FIG. 3.

[0148] In these experiments, we tested a human subject with a normalcolon alternated between breathing room air and a helium mixture withreduced oxygen. During this procedure, colon oxygenation was monitoredwith the white-LED-based probe.

[0149] Results are shown in FIG. 7. Here colon optical saturation 415begins within the normal range of values described earlier in Table 7.At time point 423, the subject inspires a helium mixture, and as aresult, at time point 426 saturation 415 begins to fall from 74% to aslow as 64%, demonstrating detection of hypoxemia. At time point 434, thesubject inspires room air, and as a result, at time point 437 saturation415 begins to recover to baseline. This pattern of detectabledesaturation is repeated during a second episode of helium inspirationat time point 445.

[0150] Use of a white LED has several unexpected advantages. First, awhite LED is very stable, even shortly after startup, in contrast to themajority of bulbs lamps that are inherently unstable. As a filament bulbwarms up, the operating temperature, and thus the light output and colorspectrum, shift. Time is required for the bulb to stabilize beforespectroscopic measurements can be made, as the reference signal (thebulb spectrum) cannot be accurately measured when the bulb spectrum ischanging (unless the reference itself is continuously sampled). Further,as a bulb ages, the tungsten filament evaporates onto the bulb glass,and changes the output. Many bulbs drop their output by over half duringtheir lifetime. Thus, during long procedures, any bulb with a shortenedlife (under 1,000 hours) suffers from significant aging, and thussignificant drift Conversely, while it is possible that a light bulb canbe made more temporally stable by lowering the electrical current, doingso increases the fraction of heat produced, dropping the luminousefficiency to under 2%. Last, arc-lamps sputter and flickersignificantly during operation as a basic characteristic of operation.Another advantage is to allow incorporation into an integrated medicalprobe, device, or system, for performing real-time spectroscopy inliving tissue in vivo. Another advantage is the high level of lightdelivered to a tissue region. Another advantage is that custom broadbandLEDs can be made from polymers embedded with different fluorescent orphosphorescent agents, while white LEDs themselves are inexpensive.Still another advantage is that the power draw of an LED is so low thatbatteries could be permanently incorporated into the LED-based probes,reducing the complexity of the plug coming from the probe and returningto the medical system monitoring a medical or surgical procedure.

Example 7

[0151] A Biocompatible Luminescence Based Source

[0152] The material in a white LED can be replaced with other fluors inorder to provide a broadband LED with unique characteristics. Forexample, Lumigen™, TPB™ (TetraPhenylButadiene), quantum dots, andothers, can be used to convert blue or UV luminescent light from aconventional LED into a broadband source. Further, significant knowledgeexists regarding how to attach and prepare Lumigen™ within amanufactured product. Lumigen™ is approved by the U.S. F.D.A. for use infood containers, Lumigen™ can withstand 220° C., so it can be depositedon fibers and then illuminated to generate fluorescent light from afiber, plastic fiber can be embedded with the Lumigen™ and can bepolished, and Lumigen™ can be deposited dissolved in a hot spray.

[0153] In summary, improved illuminators with multiple expected andunexpected advantages can therefore result from improving the deliveryefficiency of light from spectroscopic light sources to target regionsor samples. In certain applications, such as medical applications ormicrochip spectrophotometers, this improvement may need to occur withouttransferring undue heat to the sample and/or occur under space and sizeconstraints, all without degrading or with improvement in outputstability. We show that improved delivery can be achieved by either (a)improving the conversion efficiency of the source, which results in lessheat per unit energy consumed, as well as less heat produced for anygiven level of desired light delivery to the tissue, or (b) improvingthe transfer efficiency of light from the source to the sample ortissue, such as by improving the coupling efficiency of light to a lightguide or by sufficiently improving the conversion efficiency to allowthe light source to be sufficiently cool to be embedded directly next tothe sample, or both (a) and (b) together, such that the improvedilluminator can even be embedded into a medical probe or microchipspectrophotometer. Higher efficiency delivery results in a cooler, moreefficient light source, as fewer watts of power are required to producea given level of illumination at the sample. An added benefit is thatcooler sources tend to be more stable, simplifying measurements (byallowing for a single or pre-measured reference), improving data quality(by reducing reference error and sampling drift). Such improvedilluminators may permit a light source to be embedded into a device,such as into a medical probe, catheter, or monitor, as well as into amicrochip analysis system. We have discovered an improved illuminationsource for generating broadband light, and for delivering this light toa sample, with higher efficiency, and possibly with higher opticaldensity, than is achieved using conventional bare-bulb or fiber-coupledlight sources, for the purpose of enabling spectroscopic analysis. Ailluminator probe has been constructed and tested, in which aphosphor-coated white LED and integrated collimating optics have beenconstructed in accordance with the present invention to producecontinuous, broadband light from 400 nm to 700 nm in a collimated beam,which can then be transmitted through space to a sample, such as atarget tissue, resulting in a high efficiency delivery of light to thetarget region. The efficient conversion of power to light, and the highefficiency of light transfer, allow this illuminator to remain coolduring operation despite high illumination levels, further permittingthe illuminator to be integrated into the tip of a medical instrument,where then broadband illuminator can illuminate living tissue withoutdamaging the tissue. Scattered light, returning from the sample, isoptionally collected by an optical fiber integrated within the sourceoptics of the illuminator, for transfer and analysis. Medical probes andsystems incorporating the improved illuminator, and medical methods ofuse, are described. This device has been built and tested in severalconfigurations in models, animals, and humans, and has immediateapplication to several important problems, both medical and industrial,and thus constitutes an important advance in the art.

What is claimed is:
 1. A method of monitoring tissue oxygenationinvolving: (a) placing an oximeter probe on, in or near a living tissueat mucosal or subsurface tissue site; (b) illuminating the tissue with abroadband visible illumination; (c) monitoring light returning from thesubsurface or mucosal tissue cite, said light comprising at least oneset of visible wavelengths from 400 to 700 nm; and (d) determining thetissue hemoglobin oxygenation index saturation.
 2. The method of claim25 wherein said tissue site is selected from the list of tissuesconsisting of oropharynx, nasopharynx, esophagus, stomach, duodenum,ileum, colon, or other gastrointestinal mucosal or superficial tissue.3. A method of monitoring tissue oxygenation involving: (a) illuminatingthe tissue with a broadband visible illumination havingshallow-penetrating wavelengths shorter than 600 nm; (b) monitoringshallow-penetrating visible light returning from the mucosal orsubsurface tissue site; and (c) determining a tissue hemoglobinoxygenation index based upon the returning visible light.
 4. The methodof claim 3 wherein said broadband illumination comprises a portion ofthe visible spectral band from 500 nm to 600 nm.
 5. The method of claim4 wherein said medical intervention is a vascular procedure directedtoward the aorta, and said target tissue is the gastrointestinal mucosa.6. The method of claim 3 wherein said medical intervention is a vascularprocedure during which the local blood flow may change.
 7. The method ofclaim 1 wherein said probe is selected from the list of probesconsisting of catheters, clips, optical fibers, needles and wands.
 8. Avisible wavelength optical spectroscopy oximeter system comprising: (a)a broadband, low-thermal-transfer visible illumination source forilluminating a target region; (b) an optical collector for collectinglight scattered from said target region and for transmitting a collectedsignal to a spectroscopic monitor; and (c). spectroscopic monitoringmeans for receiving and analyzing collected broadband visible light as afunction of wavelength, said analysis substantially reliant uponreceived light with a wavelength below 600 nm so as to achieve ashallow, subsurface depth of penetration, and for determining an oxygensaturation index of hemoglobin in the target region based upon saidmonitored shallow penetrating visible light.
 9. The oximeter of claim 8,wherein said saturation determination is substantially performed usingcollected light in the visible violet to green spectrum from 400 to 600nm.
 10. The oximeter of claim 8, wherein said saturation determinationis substantially performed using collected light in the green to orangespectral band form 500 to 600 nm.